Per and polyfluorinated substances (PFAS) include compounds that are, or have been, manufactured in high volumes for use in a wide variety of commercial and industrial products. A subset of PFAS are of particular concern because they are very stable in the environment and accumulate in human serum/plasma. A person's internal dose can continue beyond cessation of environmental exposure. PFOA and PFOS elicit a wide variety of adverse effects in experimental models; however, epidemiological studies have observed mixed associations due to methodological limitations and challenges. The objective of our proposed project, ?A Health Study of New York State Communities Exposed to PFAS Contaminated Drinking Water?, is to complete the core protocol as prescribed by the CDC/ATSDR by developing a cohort from the greater Hoosick Falls and Newburgh communities in New York State (NYS). In Hoosick Falls, PFOA levels in the public drinking water supply were between 500 and 600 ng/L (ppt) in 2016. In Newburgh, samples of city drinking water showed PFOS levels in excess of 140 ppt, PFHxS levels in excess of 70 ppt, and PFOA levels in excess of 25 ppt. We also propose additional research projects that are responsive to these communities, while serving to enhance the core protocol and inform future PFAS related hypotheses generalizable to other communities and study sites across the U.S. For this project, we will (1) conduct historical dose reconstruction with PK modeling of serum PFAS concentrations for the greater Hoosick Falls and Newburgh communities, including historical municipal drinking water PFAS concentration modeling as needed; (2) enroll 2,175 study participants to cross- sectionally examine health endpoints related to PFAS exposure in Hoosick Falls and Newburgh; and (3) enhance the core protocol and inform future work by leveraging stored blood samples from recent PFAS biomonitoring activities in these communities to prospectively measure PFAS and related health endpoint changes over time and leveraging archived neonatal blood spots collected as part of the NYS Newborn Screening Program and vital records to measure PFAS and immune function markers among core study participants. This project will be conducted collaboratively between the University at Albany School of Public Health (UASPH) and the NYS Department of Health (NYSDOH). The UASPH was created in 1985 as a unique partnership with the NYSDOH; this partnership provides a platform for conducting large, statewide, prospective cohort studies examining emerging issues, particularly among vulnerable populations. Together, we have developed infrastructure for recruitment, tracking, and retention of our study populations. This existing infrastructure and established community relationships will be leveraged to recruit a study cohort to examine the health effects of exposure to PFAS contaminated drinking water.